Abnormal plasma lipoprotein composition in hypercholesterolaemic patients induces platelet activation

Abstract

Increased platelet activation is a feature of patients with familial hypercholesterolemia. Plasma lipoprotein concentration and composition were studied in 11 male patients with familial hypercholesterolemia and in 10 age-matched healthy controls. Increased levels of cholesterol were found in very-low- and low-density lipoproteins (53 and 275%, respectively); in high-density lipoprotein, cholesterol and apolipoprotein A-I were decreased by 21 and 26%, respectively. On incubation of gel-filtered platelets derived from normolipidemic controls with identical concentrations of lipoproteins derived from either normolipidemic controls or hypercholesterolemic patients, very-low- and low-density lipoproteins from the patients caused significantly greater thrombin-induced platelet aggregation (P < 0.01). high-density lipoprotein lipoprotein from normal subjects reduced platelet release by 22%; the patients'' high-density lipoprotein had no significant effect on platelet release. Lipoprotein-deficient plasma from both groups augmented platelet function to a similar extent. Lipoprotein composition has an important effect on platelet function in vitro. The abnormal lipid and protein composition of the lipoproteins derived from hypercholesterolemic patients appears to be the cause of platelet hyperactivity observed in these patients.